Slides ANS Overview ANS Pharmacology

Pharmacology of the Autonomic
Nervous System
With Dr. PJ Shukle
Berly Ruiz Orbezo, univer_10@hotmail.com

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ANS Overview
Medulla ACh N Parasympathetic

ACh
Cardiac and smooth muscle,
1. M
gland cells, nerve terminals

ANS Overview
1.
N
ACh ACh
M
Parasympathetic nervous system
• Preganglionic fibers originate in A. Cranial nerve nuclei III, VII, IX, X

B. Sacral segments S2-S4 of the spinal cord
• Ganglionic synapses respond to nicotine nicotinic cholinergic receptors
• Effector synapses respond to muscarine muscarinic cholinergic receptors

ANS Overview
Parasympathetic
1. Sympathetic ganglia gland cells, nerve terminals
N ACh Sympathetic
ACh
2. M Sweat glands (eccrine)
Ne Sympathetic
ACh N
a, b
3. Cardiac and smooth muscle,
ACh N
4. D Sympathetic
D1
Renal vascular smooth muscle

ANS Overview
2. 3. Ne
ACh ACh N
ACh N M a, b
4. N
ACh
D
D1
Sympathetic nervous system (2. sweat glands; 3. cardiac/vascular, glands, nerves; 4. renal)
• Preganglionic fibers originate in the thoracic and lumbar segments of the cord.
• Ganglionic synapses respond to nicotine nicotinic cholinergic receptors.
• Effector synapses respond to muscarine, noradrenaline, adrenaline, and dopamine.

ANS Overview
Parasympathetic
1. gland cells, nerve terminals
Sympathetic
2. Sweat glands (eccrine)
Sympathetic
4. Sympathetic
5. Epi, NE
N Adrenal
medulla

ANS Overview
5.
Epi, NE
N
Sympathetic adrenal system
• Preganglionic fibers originate from the thoracic segments
• Nicotinic receptors
• Adrenaline and noradrenaline into the bloodstream

ANS Overview
Parasympathetic
1. gland cells, nerve terminals
Sympathetic
2. Sweat glands (eccrine)
Sympathetic
4. Sympathetic
5.
ACh
Voluntary motor nerve N
6. Somatic
Skeletal muscle

ANS Overview
6. ACh
N
Voluntary nervous system
• Preganglionic fibers originate from the brain and all levels of the spine
• Nicotinic receptors
• Effectors are the skeletal muscles

Overview of ANS Activity
Sympathetic Nervous System Parasympathetic Nervous System
Dopaminergic Receptors Nicotinic cholinergic receptors
D1 Smooth Muscle (renal) NN Ganglia Ion channel
Adrenergic Receptors NM End Plate Ion channel
α1 Smooth Muscle, Glands
α2 Nerve, Smooth muscle Muscarinic cholinergic receptors
β1 Cardiac, juxtaglomerular M1: Nerve Endings G protein
β2 Lung, Liver M2: Heart G protein
β3 Adipocytes M3: Ciliary muscle G protein

Nonadrenergic, Noncholinergic (NANC) Transmission
Purine receptors
P1-7 Lung, GI tract, Cardiac, Urinary tract
Peptidergic
ATP adenosine triphosphate
VIP vasoactive intestinal peptide (local stimulus-response)
NPY neuropeptide Y
SUBP substance P -local-effector fibers

Examples of Dual Innervation
Dual innervation: PANS AND SANS Dual innervation: PANS AND SANS
Sympathetic activation (α1): Sympathetic activation (β1):

• Radial muscle contracts • Accelerates SA node (rate)
• Results in iris dilation (mydriasis) • Ectopic pacemakers (rate and

activity)
• Relaxes ciliary muscle (β)

Examples of Dual Innervation
Parasympathetic activity (M3): Parasympathetic activity (M2):

• Circular muscle contracts • Decelerates SA node (rate)
• Results in iris constriction • No effect on ectopic pacemakers
• Contracts ciliary muscle
Blocking BOTH systems will cause:
• Mydriasis (pupil dilation)
• Tachycardia

Effect of
Organ Sympathetic Parasympathetic
Actiona Receptorb Actiona Receptorb
Eye
Iris
Radial muscle Contracts a1
Circular muscle Contracts M3
Ciliary muscle (Relaxes) b Contracts M3
Heart
Sinoatrial node Accelerates b1, b2 Decelerates M2
Ectopic pacemakers Accelerates b1, b2
Contractility Increases b1, b2 Decreases (atria) (M2)
Blood vessels
Skin; splanchnic vessels Contracts a
Skeletal muscle vessels Relaxes b2
Contracts a
(Relaxes) (MC)
Bronchiolar smooth muscle Relaxes b2 Contracts M3
Gastrointestinal tract
Smooth muscle
Walls Relaxes a2, d b2 Contracts M3
Sphincters Contracts a1 Relaxes M3
Secretion Inhibits a2 Increases M3
Myenteric plexus Activates M1

Effect of
Organ Sympathetic Parasympathetic
Actiona Receptorb Actiona Receptorb
Genitourinary smooth muscle
Bladder wall Relaxes b2 Contracts M3
Sphincter Contracts a1 Relaxes M3
Uterus, pregnant Relaxes b2
Contracts a Contracts M3
Penis, seminal vesicles Ejaculation a Erection M
Skin
Pilomotor smooth muscle Contracts a
Sweat glands
Thermoregulatory Increases M
Apocrine (stress) Increases a
Metabolic functions
Liver Gluconeogenesis b2, a
Liver Glycogenolysis b2, a
Fat cells Lipolysis b3
Kidney Renin release b1
Autonomic nerve endings
Sympathetic ... Decreases NE release Me
Parasympathetic Decreases ACh release a

Direct Activators
α-blockers β-blockers
Phenoxybenzamine,
Nonselective Nonselective Propranolol
Phentolamine
α1 selective Prazosin β1-selective Atenolol
α2 selective Yohimbine β2-selective Butoxamine

Sympathetic Blockers
reflex:
• Blocking the ability to see in the dark

(dilation of iris)
• Blocking the creation of intraocular pressure

(secretion of aqueous humor)
Timolol, levobunolol eye drops:
• Decreased secretion of aqueous humor
• Side effect: miosis (constriction of pupil)

β-Blockers
Starting with letters A M Starting with letter C Starting with letters N Z
Tend to be more Tend to be used in Tend to be nonselective

β1-selective cardiac failure β-blockers
Acebutolol, atenolol,
Carvedilol (combined α and β Nadolol, nebivolol, pindolol,
bisoprolol, esmolol,
activity) propranolol, timolol
labetalol, metoprolol

Sympathetic Blockers
Partial agonist activity

• Are β1-blockers, but have agonist activity
on β2
• May be better in asthmatic patients
• Acebutolol, labetalol
The newest β-blocker also has activity on

nitric oxide
• Nebivolol favored by some as the best
antihypertensive

β1-Blockers
• The more selective for β1, the greater the advantage

for fewer lung side effects
• Rhythm control
• Breaking supraventricular tachycardias
• Preventing ventricular tachycardias
• Rate control in AFIB
• Heart failure (only after the patient is stabilized)
• Blood pressure
• Anxiety symptoms (propanolol)

β-Blocker Effects in Pregnancy
• Labetalol is the most used blood pressure

drug in pregnancy.
• Nice, balanced α and β activity prevents

reduced placental flow.
• Wide therapeutic window

Sympathetic Blockers: Toxicity
• Excessive bradycardia
• AV blockade
• Heart failure
• Bronchoconstriction
• Masked symptoms of hypoglycemia
• Sexual dysfunction

This document is a property of: Berly Ruiz Orbezo
Note: This document is copyright protected. It may not be copied, reproduced, used, or
distributed in any way without the written authorization of Lecturio GmbH.


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Pharmacology of the Autonomic

With Dr. PJ Shukle

Berly Ruiz Orbezo, univer_10@hotmail.com

Medulla ACh N Parasympathetic

Berly Ruiz Orbezo, univer_10@hotmail.com

Parasympathetic nervous system

• Preganglionic fibers originate in A. Cranial nerve nuclei III, VII, IX, X

• Ganglionic synapses respond to nicotine nicotinic cholinergic receptors

• Effector synapses respond to muscarine muscarinic cholinergic receptors

Berly Ruiz Orbezo, univer_10@hotmail.com

Berly Ruiz Orbezo, univer_10@hotmail.com

• Ganglionic synapses respond to nicotine nicotinic cholinergic receptors.

• Effector synapses respond to muscarine, noradrenaline, adrenaline, and dopamine.

Berly Ruiz Orbezo, univer_10@hotmail.com

Berly Ruiz Orbezo, univer_10@hotmail.com

Sympathetic adrenal system

• Preganglionic fibers originate from the thoracic segments

• Adrenaline and noradrenaline into the bloodstream

Berly Ruiz Orbezo, univer_10@hotmail.com

Berly Ruiz Orbezo, univer_10@hotmail.com

Voluntary nervous system

• Effectors are the skeletal muscles

Berly Ruiz Orbezo, univer_10@hotmail.com

Sympathetic Nervous System Parasympathetic Nervous System

Dopaminergic Receptors Nicotinic cholinergic receptors

D1 Smooth Muscle (renal) NN Ganglia Ion channel

Adrenergic Receptors NM End Plate Ion channel

α1 Smooth Muscle, Glands

α2 Nerve, Smooth muscle Muscarinic cholinergic receptors

β1 Cardiac, juxtaglomerular M1: Nerve Endings G protein

β2 Lung, Liver M2: Heart G protein

β3 Adipocytes M3: Ciliary muscle G protein

Berly Ruiz Orbezo, univer_10@hotmail.com

Nonadrenergic, Noncholinergic (NANC) Transmission

P1-7 Lung, GI tract, Cardiac, Urinary tract

ATP adenosine triphosphate

VIP vasoactive intestinal peptide (local stimulus-response)

SUBP substance P -local-effector fibers

Berly Ruiz Orbezo, univer_10@hotmail.com

Sympathetic activation (α1): Sympathetic activation (β1):

• Results in iris dilation (mydriasis) • Ectopic pacemakers (rate and

Berly Ruiz Orbezo, univer_10@hotmail.com

Parasympathetic activity (M3): Parasympathetic activity (M2):

• Results in iris constriction • No effect on ectopic pacemakers

• Contracts ciliary muscle

Blocking BOTH systems will cause:

• Mydriasis (pupil dilation)

Berly Ruiz Orbezo, univer_10@hotmail.com

Berly Ruiz Orbezo, univer_10@hotmail.com

Berly Ruiz Orbezo, univer_10@hotmail.com

α1 selective Prazosin β1-selective Atenolol

α2 selective Yohimbine β2-selective Butoxamine

Berly Ruiz Orbezo, univer_10@hotmail.com

• Blocking the ability to see in the dark

• Blocking the creation of intraocular pressure

Timolol, levobunolol eye drops:

• Decreased secretion of aqueous humor

• Side effect: miosis (constriction of pupil)

Berly Ruiz Orbezo, univer_10@hotmail.com

Starting with letters A M Starting with letter C Starting with letters N Z

Tend to be more Tend to be used in Tend to be nonselective

Berly Ruiz Orbezo, univer_10@hotmail.com

Partial agonist activity

• May be better in asthmatic patients